All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma

Meletios A. Dimopoulos, Sebastian Grosicki, Wiesław W. Jędrzejczak, Hareth Nahi, Astrid Gruber, Markus Hansson, Neeraj Gupta, Catriona Byrne, Richard Labotka, Zhaoyang Teng, Huyuan Yang, Norbert Grzasko, Shaji K Kumar

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Abstract

Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalEuropean Journal of Cancer
Volume106
DOIs
StatePublished - Jan 1 2019

Fingerprint

Multiple Myeloma
Cyclophosphamide
Dexamethasone
Transplants
Maintenance
Arm
Therapeutics
ixazomib
Neutropenia
Disease-Free Survival
Safety

Keywords

  • Elderly
  • Multiple myeloma
  • Newly diagnosed
  • Oral therapy
  • Transplant-ineligible

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. / Dimopoulos, Meletios A.; Grosicki, Sebastian; Jędrzejczak, Wiesław W.; Nahi, Hareth; Gruber, Astrid; Hansson, Markus; Gupta, Neeraj; Byrne, Catriona; Labotka, Richard; Teng, Zhaoyang; Yang, Huyuan; Grzasko, Norbert; Kumar, Shaji K.

In: European Journal of Cancer, Vol. 106, 01.01.2019, p. 89-98.

Research output: Contribution to journalArticle

Dimopoulos, MA, Grosicki, S, Jędrzejczak, WW, Nahi, H, Gruber, A, Hansson, M, Gupta, N, Byrne, C, Labotka, R, Teng, Z, Yang, H, Grzasko, N & Kumar, SK 2019, 'All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma' European Journal of Cancer, vol. 106, pp. 89-98. https://doi.org/10.1016/j.ejca.2018.09.011
Dimopoulos, Meletios A. ; Grosicki, Sebastian ; Jędrzejczak, Wiesław W. ; Nahi, Hareth ; Gruber, Astrid ; Hansson, Markus ; Gupta, Neeraj ; Byrne, Catriona ; Labotka, Richard ; Teng, Zhaoyang ; Yang, Huyuan ; Grzasko, Norbert ; Kumar, Shaji K. / All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. In: European Journal of Cancer. 2019 ; Vol. 106. pp. 89-98.
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abstract = "Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66{\%} of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21{\%} of patients discontinued treatment during induction and 3{\%} during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25{\%}, and overall response rate (ORR) was 73{\%}. Including the maintenance phase, CR+VGPR rate was 33{\%}, and ORR was 76{\%}. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31{\%}). Grade ≥3 AEs were reported by 73{\%} of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.",
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T1 - All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma

AU - Dimopoulos, Meletios A.

AU - Grosicki, Sebastian

AU - Jędrzejczak, Wiesław W.

AU - Nahi, Hareth

AU - Gruber, Astrid

AU - Hansson, Markus

AU - Gupta, Neeraj

AU - Byrne, Catriona

AU - Labotka, Richard

AU - Teng, Zhaoyang

AU - Yang, Huyuan

AU - Grzasko, Norbert

AU - Kumar, Shaji K

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.

AB - Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.

KW - Elderly

KW - Multiple myeloma

KW - Newly diagnosed

KW - Oral therapy

KW - Transplant-ineligible

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